Continuing the Debate Over Viral Contributions to Alzheimer's Disease

Persistent viral infection may be an important contributing cause of Alzheimer's disease, either because the amyloid-β associated with Alzheimer's disease is a part of the innate immune response, and infection thereby increases production, or because persistent infection drives the chronic inflammation that disrupts the biochemistry of brain tissue. If viral infection does drive Alzheimer's disease, it may go some way towards explaining why the disease doesn't correlate with lifestyle factors such as weight, activity, and so forth, anywhere near as well as is the case for other common age-related conditions. It all sounds plausible, and the various mechanisms that may be involved certainly exist, but the supporting evidence from patient data is so far mixed, despite a few quite compelling studies. The hypothesis is by no means concretely demonstrated, but researchers here suggest that pathology may require multiple viruses, a possible explanation for confounding data in studies that only focus on one type of viral infection.

Using a three-dimensional human tissue culture model mimicking the brain, researchers have shown that varicella zoster virus (VZV), which commonly causes chickenpox and shingles, may activate herpes simplex (HSV), another common virus, to set in motion the early stages of Alzheimer's disease. Normally HSV-1 - one of the main variants of the virus - lies dormant within the neurons of the brain, but when it is activated it leads to accumulation of tau and amyloid beta proteins, and loss of neuronal function, signature features found in patients with Alzheimer's.

Researchers re-created brain-like environments in small 6 millimeter-wide donut-shaped sponges made of silk protein and collagen. They populated the sponges with neural stem cells that grow and become functional neurons capable of passing signals to each other in a network, just as they do in the brain. Some of the stem cells also form glial cells, which are typically found in the brain and help keep the neurons alive and functioning.

The researchers found that neurons grown in the brain tissue can be infected with VZV, but that alone did not lead to the formation of the signature Alzheimer's proteins tau and beta-amyloid - the components of the tangled mess of fibers and plaques that form in Alzheimer's patients' brains - and that the neurons continued to function normally. However, if the neurons already harbored quiescent HSV-1, the exposure to VZV led to a reactivation of HSV, and a dramatic increase in tau and beta-amyloid proteins, and the neuronal signals begin to slow down. "It's a one-two punch of two viruses that are very common and usually harmless, but the lab studies suggest that if a new exposure to VZV wakes up dormant HSV-1, they could cause trouble."



how do we get rid of VZV and HSV?

Posted by: erasmus at August 5th, 2022 5:46 AM

Are there too many side effects of taking an antiviral medication chronically?

We already have these medicines such as acyclovir, etc. However... does acyclovir clear an existing infection? from what I can read it seems to prevent the spread of the virus. So your immune system + acyclovir could slowly clear the infection?

Posted by: Matt at August 5th, 2022 7:11 AM

Thanks erasmus for that question.
And thanks Antonio for reply/ link to that question. It gives me hope:) Hopefully it won't take too long, though, not getting any younger.

Posted by: Robert at August 5th, 2022 12:33 PM

Most Pathways Can Be Related to the Pathogenesis of Alzheimer's Disease

"Alzheimer's disease (AD) is a complex neurodegenerative disorder. The relative contribution of the numerous underlying functional mechanisms is poorly understood. To comprehensively understand the context and distribution of pathways that contribute to AD, we performed text-mining to generate an exhaustive, systematic assessment of the breadth and diversity of biological pathways within a corpus of 206,324 dementia publication abstracts. A total of 91% (325/335) of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways have publications containing an association via at least 5 studies, while 63% of pathway terms have at least 50 studies providing a clear association with AD. Despite major technological advances, the same set of top-ranked pathways have been consistently related to AD for 30 years, including AD, immune system, metabolic pathways, cholinergic synapse, long-term depression, proteasome, diabetes, cancer, and chemokine signaling. AD pathways studied appear biased: animal model and human subject studies prioritize different AD pathways. Surprisingly, human genetic discoveries and drug targeting are not enriched in the most frequently studied pathways. Our findings suggest that not only is this disorder incredibly complex, but that its functional reach is also nearly global. As a consequence of our study, research results can now be assessed in the context of the wider AD literature, supporting the design of drug therapies that target a broader range of mechanisms. The results of this study can be explored at"

Posted by: Jones at August 7th, 2022 5:17 AM
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